Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1.
Besra, Gurdyal S
Cook, Charlotte N
Cunningham, Adam F
Nature Publishing Group
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Newman, R., Ahlfors, H., Saveliev, A., Galloway, A., Hodson, D., Williams, R., Besra, G. S., et al. (2017). Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1.. Nature immunology, 18 683-693. https://doi.org/10.1038/ni.3724
RNA-binding proteins of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU-rich elements in the 3' untranslated region and promoting mRNA decay. Here we identified an indispensable role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal-zone B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene-expression program related to signaling, cell adhesion and locomotion; it achieved this in part by limiting expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype. These mechanisms emphasize the importance of integrating transcriptional and post-transcriptional processes by RNA-binding proteins for maintaining cellular identity among closely related cell types.
Lymphoid Tissue, B-Lymphocytes, Animals, Mice, RNA-Binding Proteins, Nuclear Proteins, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Sequence Analysis, RNA, Cell Adhesion, Signal Transduction, Cell Movement, Gene Expression Regulation, Phenotype, Interferon Regulatory Factors, Kruppel-Like Transcription Factors, High-Throughput Nucleotide Sequencing, Real-Time Polymerase Chain Reaction
This work was funded by a GSK-CASE studentship to RN and funding from the Biotechnology and Biological Sciences Research Council, The Medical Research Council and Bloodwise.
Medical Research Council (MR/M008584/1)
External DOI: https://doi.org/10.1038/ni.3724
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264475